TY - JOUR
T1 - A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury
AU - Gomez, Hernando
AU - Ince, Can
AU - de Backer, Daniel
AU - Pickkers, Peter
AU - Payen, Didier
AU - Hotchkiss, John
AU - Kellum, John A.
PY - 2014
Y1 - 2014
N2 - Given that the leading clinical conditions associated with acute kidney injury (AKI), namely, sepsis, major surgery, heart failure, and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macrohemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow. Accordingly, renal injury may not be entirely explained solely on the basis of the classic paradigm of hypoperfusion, and thus other mechanisms must come into play. Herein, we put forward a "unifying theory" to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria, and that it ultimately results in and explains the clinical phenotype of sepsis-induced AKI
AB - Given that the leading clinical conditions associated with acute kidney injury (AKI), namely, sepsis, major surgery, heart failure, and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macrohemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow. Accordingly, renal injury may not be entirely explained solely on the basis of the classic paradigm of hypoperfusion, and thus other mechanisms must come into play. Herein, we put forward a "unifying theory" to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria, and that it ultimately results in and explains the clinical phenotype of sepsis-induced AKI
U2 - https://doi.org/10.1097/SHK.0000000000000052
DO - https://doi.org/10.1097/SHK.0000000000000052
M3 - Review article
C2 - 24346647
SN - 1073-2322
VL - 41
SP - 3
EP - 11
JO - Shock (Augusta, Ga.)
JF - Shock (Augusta, Ga.)
IS - 1
ER -